When protamine and heparin are administered to rats intravenously, electron dense aggregates appear on the epithelial side of the glomerular basement membrane. We have previously shown these deposits to contain protamine and evidence supports the assumption that they are protamine-heparin aggregates. We are studying the phenomenon of the disappearance of these aggregates in order to determine the role of the glomerular visceral epithelial cell as an endocytic cell. We have shown, in vivo, that the protamine-heparin aggregates disappear according to the first order kinetics and that this disappearance rate is not effected by acute ureteral obstruction. We are currently carrying out studies in order to define the mechanism responsible for this disappearance. Utilizing an in vitro system of isolated glomeruli, we are measuring the effect of temperature, metabolic poisons such as sodium fluoride and cyanide and inhibitors of phagocytosis such as cytochalasin B, upon the disappearance of protamine-heparin aggregates from the glomerular basement membrane. Insofar as our initial in vivo and in vitro studies supported glomerular epithelial cell endocytosis as the cause for the disappearance of aggregates, we are studying rats with various experimental glomerular diseases in order to determine whether the epithelial cell functions normally in these states. Rats with chronic autologous immune complex glomerulonephritis, aminonucleoside nephrosis, nephrotoxic (anti-GBM) nephritis, and overload proteinuria are being studied and disappearance curves constructed at various stages of these lesions. Studies are also being carried out to determine whether the chronic administration or protamine-heparin aggregates alters the disappearance kinetics in order to determine whether this mechanism can be stimulated.